HDAC7 promotes NSCLC proliferation and metastasis via stabilization by deubiquitinase USP10 and activation of β-catenin-FGF18 pathway

作者：Kai Guo, Zhiqiang Ma, Yujiao Zhang, Lu Han, Changjian Shao, Yingtong Feng, Fei Gao, Shouyin Di, Zhipei Zhang, Jiao Zhang, Fabrizio Tabbò, Simon Ekman, Kenichi Suda, Federico Cappuzzo, Jing Han, Xiaofei Li, Xiaolong Yan · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2022 · DOI：10.1186/s13046-022-02266-9 · 被引用次数：64 · 研究领域：Histone Deacetylase Inhibitors Research、Fibroblast Growth Factor Research、Epigenetics and DNA Methylation

BACKGROUND: Histone deacetylases (HDACs) play crucial roles in cancers, but the role and mechanism of HDAC7 in NSCLC have not been fully understood. METHODS: A total of 319 patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study. Immunohistochemistry and Kaplan-Meier survival analysis were performed to investigate the relationship between HDAC7, fibroblast growth factor 18 (FGF18) expression, and clinicopathologic characteristics. Cell functional experiments were implemented both in vivo and in vitro to investigate the effects on NSCLC cell proliferation and metastasis. Recombinant lentivirus-meditated in vivo gene overexpression or knockdown, real-time polymerase chain reaction (PCR), western blotting, and coimmunoprecipitation assays were applied to clarify the underlying molecular mechanism of HDAC7 in promoting NSCLC progression. RESULTS: The elevated expression of HDAC7 or FGF18 was positively correlated with poor prognosis, tumor-node-metastasis (TNM) stage, and tumor differentiation of NSCLC patients. NSCLC patients with co-expressed HDAC7 and FGF18 suffered the worst prognosis. HDAC7 overexpression promoted NSCLC proliferation and metastasis by upregulating FGF18. Conversely, overexpression of FGF18 reversed the attenuated ability in tumor growth and metastasis mediated by downregulating HDAC7. In terms of mechanism, our results suggested that the interaction of HDAC7 with β-catenin caused decreased β-catenin acetylation leve...